Identification of intronic-splice site mutations in GATA4 gene in Indian patients with congenital heart disease.

Congenital Heart Disease (CHD) is the most common birth defect among congenital anomalies that arise before birth. GATA4 transcription factor plays an important role in foetal heart development. Mutational analysis of GATA4 gene in CHD patients revealed five known heterozygous mutations (p.T355S, p.S377G, p.V380M, p.P394T and p.D425N) identified in exons 5 and 6 regions and fifteen intronic variants in the non-coding regions (g.76885T>C/Y,g.76937G>S, g.78343G>R, g.83073T>Y, g.83271C>A/M, g.83318G>K, g.83415G>R, g.83502A>C/M, g.84991G>R, g.85294C>Y, g.85342C>T/Y, g.86268A>R, g.87409G>A/R, g.87725T>Y, g.87813A>T/W). In silico analysis of these intronic variants identified two potential branch point mutations (g.83271C>A/M, g.86268A>R) and predicted effects of these on intronic splice sites as enhancer and silencer motifs. This study attempts to correlate the pattern of intronic variants of GATA4 gene which might provide new insights to unravel the possible molecular etiology of CHD.

Molecular Delineation of Partial Trisomy 14q and Partial Trisomy 12p in a Patient with Dysmorphic Features, Heart Defect and Developmental Delay.

This study describes a molecular analysis of partial trisomy 14q and partial trisomy 12p in a 5-year-old male child presenting with dysmorphic features, congenital heart disease and global developmental delay. Chromosomal analysis of the patient with GTG bands revealed a 47,XY,+der(14)t(12;14)(p13;q22)mat karyotype; the mother's karyotype was 46,XX,t(12;14)(p13;q22). Further, oligonucleotide array- CGH studies revealed an amplification of 32.3 Mb in the 14q11.1q22.1 region, substantiating partial trisomy 14q and additionally displaying an amplification of ∼1 Mb in the 12p13.3pter region for partial trisomy 12p. This is the first study to demonstrate a novel association of partial trisomies of 14q and 12p due to a 3:1 segregation of a maternal balanced translocation involving chromosomes 12 and 14. Gene ontology studies indicated 5 potential candidate genes in the amplified regions for the observed congenital anomalies.

A novel mutation in the transglutaminase-1 gene in an autosomal recessive congenital ichthyosis patient.

Structure-function implication on a novel homozygous Trp250/Gly mutation of transglutaminase-1 (TGM1) observed in a patient of autosomal recessive congenital ichthyosis is invoked from a bioinformatics analysis. Structural consequences of this mutation are hypothesized in comparison to homologous enzyme human factor XIIIA accepted as valid in similar structural analysis and are projected as guidelines for future studies at an experimental level on TGM1 thus mutated.

Glycemic control modifies the association between microalbuminuria and c-reactive protein in Type 2 Diabetes Mellitus.

Microalbuminuria and C-reactive protein reflect closely related components of the same disease process. The present study attempts to evaluate whether any association exists between C-reactive protein and microalbuminuria in Type 2 Diabetes Mellitus patients with poor and adequate glycemic control. It was observed that in diabetics with poor glycemic control, microalbuminuria showed a significant positive correlation with C-reactive protein and the prevalence of microalbuminuria was significantly more at elevated C-reactive protein levels. These parameters were not significant in subjects with adequately controlled disease. Further, there was a significant increase in levels of microalbuminuria in patients with poor glycemic control when compared to well-controlled diabetics at comparative levels of C-reactive protein. This study supports the hypothesis that endothelial dysfunction and inflammatory activity are involved in the pathogenesis of microalbuminuria and underscores the importance of glycemic control in the progression of inflammation in diabetes.